The analysis of hair for drugs of abuse is of interest in toxicology, and to determine compliance or recidivism in patients in drug-abuse treatment programs, to provide a scientific marker for epidemiological studies of drug abuse, to serve as a deterrent to drug usage by fear of detection, and to aid in the detection of potential drug exposure in newborns by drug detection in the mother during pregnancy and in the newborn at birth. It is probable that drugs can be detected in hair at times when the plasma does not contain measurable concentrations of drugs. Thus, there is a greater need to establish the basic pharmacologic principles of dose- response and time-response for the concentration of drugs of abuse in human hair. To establish these principles the aims of this project are: 1) To develop ultra-sensitive, selective and reliable gas chromatography/mass spectrometry methods to measure drugs of abuse in hair. Each method will be evaluated for removal of surface-absorbed contaminants, enzymatic or alkaline digestion of hair, selective extraction of drugs and/or metabolites, conversion of the drugs to derivatives well-suited for GC/MS analysis, and analysis of the derivatized drugs by gas chromatography/ion trap mass spectrometry; 2) To develop and validate relevant models of in vitro human hair culture and of human scalp skin (containing hair) transplanted to nude mice. The model of human scalp skin containing hair will be validated for dose-response and time-response relationships by similar studies in human subjects. This model will be used to study, in detail, the factors that control the concentration of drugs in hair; and 3) To develop a model for the study of the pharmacokinetics of drugs of abuse in the hair of human subjects. Codeine will be administrated to male and female human subjects in single, increasing doses and multiple doses to determine the dose-response and time-response relationships with drug concentrations in hair. The effect of hair color and racial and ethnic background on drug concentration in hair will also be determined. Preliminary data presented with this proposal demonstrate that we are able to quantitate morphine in human hair obtained from heroin users and that we are able graft human scalp skin, containing hair follicles, to nude mice. Experiments to achieve the above aims will provide data for the careful, scientific study of the factors controlling the disposition of drugs of abuse in human hair.